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Background Interventions focused on weight loss can prevent, delay, and improve management of type 2 diabetes (T2D). However, implementation of these programs is challenging in diverse populations. South Asians have higher risk for T2D, yet to date, there have been limited programs for this community in the USA. The aim of this project was to develop and test the feasibility of a tailored group visit model for Bangladeshis with type 2 diabetes (T2D) or prediabetes based in primary care. Design Mixed-methods single-arm feasibility study. Setting An academic health center-based primary care clinic in Atlanta, Georgia. Participants Bangladeshi adults > 18 years old with T2D or prediabetes Methods In conjunction with a community-academic board, we conducted focus groups to tailor an existing evidence-based curriculum to a culturally acceptable intervention. Fourteen participants enrolled in the 16-week program focusing on healthy diet, exercise, and weight loss. The primary feasibility outcomes were number of sessions attended and participant satisfaction with the intervention. Weight, blood pressure, cholesterol, and HbA1C were measured at beginning and end of study. Participants were asked to evaluate each session on level of satisfaction. One tailed paired t tests were used to test significance of pre-post changes in outcomes. Results Key themes from the formative focus groups (n = 50) were closely tied to sociocultural beliefs and included: dietary patterns, physical activity perceptions, and healthcare access concerns. In the intervention, 10 of 14 participants had baseline and follow-up data. Participant attendance averaged 50%. Statistically significant reductions in mean weight (− 2%, 95%CI: − 3.1, 0.2 kg), systolic/diastolic blood pressure (− 12.7 mmHg [95%CI: − 23.2, − 2.2]/− 3.7 mmHg [95%CI: − 7.6, − 0.1], respectively), and triglycerides (− 62.6 mg/dl, 95%CI: − 123.1, − 2.0) were noted. Overall, participants reported high levels of satisfaction with the program. Conclusion A lifestyle program based in primary care is feasible and acceptable for Bangladeshi immigrants. Larger studies testing the effectiveness of group programs, in primary care, to improve cardiometabolic factors are important. Trials registration ClinicalTrials.gov; NCT03861546. Registered 28 February 2019.

OBJECTIVE Diabetes prevalence is increasing rapidly in rural areas of low- and middle-income countries (LMICs), but there are limited data on the performance of health systems in delivering equitable and effective care to rural populations. We therefore assessed rural-urban differences in diabetes care and control in LMICs. RESEARCH DESIGN AND METHODS We pooled individual-level data from nationally representative health surveys in 42 countries. We used Poisson regression models to estimate age-adjusted differences in the proportion of individuals with diabetes in rural versus urban areas achieving performance measures for the diagnosis, treatment, and control of diabetes and associated cardiovascular risk factors. We examined differences across the pooled sample, by sex, and by country. RESULTS The pooled sample from 42 countries included 840,110 individuals (35,404 with diabetes). Compared with urban populations with diabetes, rural populations had ∼15–30% lower relative risk of achieving performance measures for diabetes diagnosis and treatment. Rural populations with diagnosed diabetes had a 14% (95% CI 5–22%) lower relative risk of glycemic control, 6% (95% CI −5 to 16%) lower relative risk of blood pressure control, and 23% (95% CI 2–39%) lower relative risk of cholesterol control. Rural women with diabetes had lower achievement of performance measures relating to control than urban women, whereas among men, differences were small. CONCLUSIONS Rural populations with diabetes experience substantial inequities in the achievement of diabetes performance measures in LMICs. Programs and policies aiming to strengthen global diabetes care must consider the unique challenges experienced by rural populations.

ImportanceConsistent medication use is critical for diabetes management. Population surveillance of consistency of medication use may identify opportunities to improve diabetes care.ObjectiveTo evaluate trends in longitudinal use of glucose-, blood pressure–, and lipid-lowering medications by adults with diabetes.Design, Setting, and ParticipantsThis serial cross-sectional study assessed trends in longitudinal use of glucose-, blood pressure–, and lipid-lowering medications by adults with diagnosed diabetes participating in the Medical Expenditure Panel Survey (MEPS), which allows serial cross-sections and 2-year longitudinal follow-up, between the 2005 to 2006 panel and 2018 to 2019 panel. Population-weighted, nationally representative estimates for the US were reported. Included individuals were adult MEPS participants with diagnosed diabetes during both years (ie, during 2005 and 2006 or during 2018 and 2019) who participated in all survey rounds. Data were analyzed from August 2021 to November 2022.Main Outcomes and MeasuresLongitudinal use over the 2 years was categorized as continued use (at least 1 fill per year), no use, inconsistent use, and new use by medication type (glucose-, blood pressure–, and lipid-lowering medications). New medications were defined as prescription fills for a medication type first prescribed and filled in year 2 of MEPS participation.ResultsA total of 15 237 participants with diabetes (7222 individuals aged 45-64 years [47.4%]; 8258 [54.2%] female participants; 3851 Latino [25.3%]; 3619 non-Latino Black (23.8%), and 6487 non-Latino White [42.6%]) were included in the analytical sample. A mean of 19.5% (95% CI, 18.6%-20.3%), 17.1% (95% CI, 16.2%-18.1%), and 43.3% (95% CI, 42.2%-44.3%) of participants did not maintain continuity in use of glucose-, blood pressure–, or lipid-lowering medications, respectively, during both years of follow-up. The proportion of participants who continued use of glucose-lowering medication in both years trended down from 84.5% (95% CI, 81.8%-87.3%) in 2005 to 2006 to 77.4% (95% CI, 74.8%-80.1%) in 2018 to 2019; this decrease coincided with rate increases in inconsistent use (3.3% [95% CI, 1.9%-4.7%] in 2005-2006 to 7.1% [95% CI, 5.6%-8.6%] in 2018-2019) and no use (8.1% [95% CI, 6.0%-10.1%] in 2005-2006 to 12.9% [95% CI, 10.9%-14.9%] in 2018-2019). Inconsistent use of blood pressure–lowering medications trended upward from 3.9% (95% CI, 1.8%-6.0%) in 2005 to 2006 to 9.0% (95% CI, 7.0%-11.0%) in 2016 to 2017. Inconsistent use of lipid-lowering medication trended up to a high of 9.9% (95% CI, 7.0%-12.7%) in 2017 to 2018.Conclusions and RelevanceThis study found that a mean of 19.5% of participants did not maintain continuity in use of glucose-lowering medication, with recent decreases, while a mean of 17.1% and 43.2% of participants did not maintain continuity of use of blood pressure– or lipid-lowering medications, respectively.

International audience; Obesity develops in a substantial number of people initiating and maintaining modern antiretroviral therapy. The comorbidities associated with obesity make significant weight gain and metabolic changes a major consideration in clinical trials studying different regimens' potency and safety. It is as yet unclear what role individual antiretrovirals or classes play in weight gain but the issue is a complex one for clinical trial design, especially when deciding when "too much" weight has been gained, in a context where we do not yet know if switching to alternative regimens will slow, halt or reverse weight gain or metabolic changes. In addition, clinician and trial participant opinion on acceptable weight gain may differ. We offer preliminary guidance for discussion for future antiretroviral clinical trial design.

Objective: We assessed the impact of a collaborative care intervention on anxiety symptoms among participants in India with comorbid depression, poorly controlled diabetes, and moderate to severe anxiety symptoms. Method: We analyzed data from a randomized controlled trial conducted at four diabetes clinics in India. Participants received either collaborative care or usual care. We included only participants who scored ⩾10 on the Generalized Anxiety Disorder-7 (GAD-7) at baseline. We estimated the effect of the intervention on clinically significant reduction in anxiety symptoms; we considered several potential baseline moderators and mediation by anti-depressant use. Results: One hundred and seventy-two participants scored 10 or above on the GAD-7 at baseline. Collaborative care participants were more likely than control participants to achieve a clinically significant reduction in anxiety symptoms at 6 and 12 months (65.7% vs. 41.4% at 12 months, p = 0.002); these differences were not sustained at 18 or 24 months. There was little evidence of moderation by participant characteristics at baseline, and effects were not mediated by anti-depressant use. Conclusions: Collaborative care for the treatment of depression and type 2 diabetes can lead to clinically significant reductions in anxiety symptoms among patients with anxiety. Effects were notable during the active intervention period but not over the year post-intervention.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

Introduction: Although there is literature on missed diagnoses of acute coronary syndrome (ACS) in the Emergency Department (ED), and on avoidable admissions to hospitals, no previous studies have examined racial disparities in hospitalization rates among patients who received a discharge code of ACS in the ED. Hypothesis: We hypothesized that Non-White patients are more likely to be discharged home with a diagnosis of ACS than White individuals, and that health insurance, as a mediator, drives racial disparities in these hospitalization rates. Methods: We examined 51,022,910 discharge records of ED visits in Florida, New York, and Utah in years 2008, 2011, 2014, 2016/7, using state-specific data from the Healthcare Cost and Utilization Project. We identified ED admissions for acute myocardial infarction (AMI) or unstable angina using the International Classification of Disease ninth or tenth revision diagnosis codes, excluding those with chronic coronary heart disease to examine incident events only. We used generalized estimating equation models to compare risks of being sent home across race/ethnic groups including White, Black, Hispanic, and Asian/Pacific Islander patients. We used inverse probability weighting to estimate the mediating role of health insurance status on the associations. Results: Among 235,936 patients who visited the ED and received a discharge code of ACS in the study period, the proportion discharged home was 12 % among Black patients, 6 % among White patients, 9 % among Hispanic patients, and 9 % among Asian or Pacific islander patients. In age and sex-adjusted models the incidence risk ratio (IRR) for being discharged home was 1.3 (95% CI, 1.2 - 1.3) in Black patients 1.2 (95 % CI, 1.1 - 1.3) in Hispanic patients and 1.1 (95% CI, 0.9 -1.3) in Asian or Pacific Islander patients compared with White patients. Health insurance status did not play any role as a mediator. In patients below 55 years of age, differences were magnified for all racial groups compared to White patients. Conclusions: Racial disparities exist in hospitalization of AMI at the ED, which are especially marked among younger patients. Health insurance does not explain these racial differences; other possible causes need to be investigated.

Objectives The Government of India prohibited the sale of tobacco products during the COVID-19 lockdown to prevent spread of the SARS-CoV-2 virus. This study assessed the tobacco cessation behaviour and its predictors among adult tobacco users during the initial COVID-19 lockdown period in India. Study design : Cross-sectional study. Methods A cross-sectional study was conducted with 801 adult tobacco users (both smoking and smokeless tobacco) in two urban metropolitan cities of India over a 2-month period (July–August 2020). The study assessed complete tobacco cessation and quit attempts during the lockdown period. Logistic and negative binomial regression models were used to study correlates of tobacco cessation and quit attempts, respectively. Results In total, 90 (11.3%) tobacco users reported that they had quit using tobacco after the COVID-19 lockdown period. Overall, a median of two quit attempts (interquartile range [IQR] 0–6) were made by tobacco users. Participants with good knowledge on the harmful effects of tobacco use and COVID-19 were significantly more likely to quit tobacco use (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.2–4.0) and reported more quit attempts (incidence risk ratio [IRR] 5.7; 95% CI 2.8-11.8] compared with those with poor knowledge. Participants who had access to tobacco products were less likely to quit tobacco use compared with those who had no access (OR 0.3; 95% CI 0.2–0.5]. Conclusions Access restrictions and correct knowledge on the harmful effects of tobacco use and COVID-19 can play an important role in creating a conducive environment for tobacco cessation among users.

OBJECTIVE We characterized annual trends of severe hypoglycemic and hyperglycemic crises (diabetic ketoacidosis/hyperglycemic hyperosmolar state) in patients with diabetes and end-stage kidney disease (ESKD). RESEARCH DESIGN AND METHODS This was a nationwide, retrospective study of adults (≥18 years old) with diabetes/ESKD, from the United States Renal Data System registry, between 2013 and 2017. Primary outcome was annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1,000 person-years. Event rates and risk factors were adjusted for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen, and U.S. region. RESULTS Among 521,789 adults with diabetes/ESKD (median age 65 years [interquartile range 57–73], 56.1% male, and 46% White), overall adjusted rates of hypoglycemic and hyperglycemic crises were 53.64 and 18.24 per 1,000 person-years, respectively. For both hypoglycemia and hyperglycemia crises, respectively, the risks decreased with age and were lowest in older patients (≥75 vs. 18–44 years old: incidence rate ratio 0.35, 95% CI 0.33–0.37, and 0.03, 0.02–0.03), women (1.09, 1.06–1.12, and 1.44, 1.35–1.54), and those with smoking (1.36, 1.28–1.43, and 1.71, 1.53–1.91), substance abuse (1.27, 1.15–1.42, and 1.53, 1.23–1.9), retinopathy (1.10, 1.06–1.15, and 1.36, 1.26–1.47), and insulin therapy (vs. no therapy; 0.60, 0.59–0.63, and 0.44, 0.39–0.48). For hypoglycemia, specifically, additional risk was conferred by Black race (1.11, 1.08–1.15) and amputation history (1.20, 1.13–1.27). CONCLUSIONS In this nationwide study of patients with diabetes/ESKD, hypoglycemic crises were threefold more common than hyperglycemic crises, greatly exceeding national reports in nondialysis patients with chronic kidney disease. Young, Black, and female patients were disproportionately affected.

Diabetes and hypertension are common in Asian Americans and vary by subgroup. There may be further variation by social determinants of health (SDOHs), but few studies have examined this previously.To examine the associations of SDOHs and diabetes and hypertension within and across Asian subgroups in the USA DESIGN: Series cross-sectional analyses SETTING: National Health Interview Surveys (NHIS) from 1999 to 2018 PARTICIPANTS: Asian-American adults (Chinese, Filipino, Asian Indian, and Other Asian [Korean, Vietnamese, Japanese, and other]) MEASUREMENTS: Self-reported diabetes and hypertension prevalence in pooled 5-year increments over 1999-2018 and multivariable regression models to assess the adjusted prevalence of diabetes or hypertension by poverty, marital status, education, and years in the USA, adjusting for age, sex, BMI, and health insurance status RESULTS: From 1999-2003 to 2014-2018, the age- and sex-adjusted prevalence of diabetes increased for Other Asians (absolute change: 4.6%) but not for other subgroups; age- and sex-adjusted hypertension prevalence significantly increased for Asian Indians and Other Asians (absolute change: 5-7.5%). For Filipinos, high school education or less was associated with an increase in diabetes prevalence over time (difference from 1999-2003 to 2014-2018: +6.0 (95% CI: 2.0-10.0)), while for Asian Indians, college education or higher was associated with an increase in diabetes prevalence for the same period (difference: +2.7 (95% CI: 0.01-5.4). Differences over the 2 time periods (1999-2003 and 2014-2018) show that Filipino and Other Asians, who lived in the USA for ≥10 years, increased in diabetes prevalence. Similar variations in associations of SDOHs by Asian subgroup were seen for hypertension.Self-reported primary outcomes and multi-year data were pooled due to small sample sizes.The influence of SDOHs on cardiometabolic risk is not uniform among Asian Americans, implying tailored strategies may be needed for different population subgroups.NIH.

Diabetes is an increasingly common, progressive metabolic disorder that results in a range of distressing symptoms, altered daily functioning, social and psychological impacts on individuals and their families, high healthcare expenditures, lost productivity, and premature mortality. Prevalence and absolute numbers of people with diabetes has grown worldwide, with no country or region spared. In this chapter, we review the data regarding diabetes burdens, describing patterns observed in low- and middle-income countries, and in high-income countries. We describe the major gaps that must be addressed, both in research and in implementation, to better detect, prevent, and treat diabetes. We describe what is known and yet unknown about vulnerable populations and describe efforts to address disparities in diabetes.

Background The growing burden of hypertension and diabetes is one of the major public health challenges being faced by the health system in India. Clinical Decision Support Systems (CDSS) that assist with tailoring evidence-based management approaches combined with task-shifting from more specialized to less specialized providers may together enhance the impact of a program. We sought to integrate a technology “CDSS” and a strategy “Task-shifting” within the Government of India’s (GoI) Non-Communicable Diseases (NCD) System under the Comprehensive Primary Health Care (CPHC) initiative to enhance the program’s impact to address the growing burden of hypertension and diabetes in India. Methods We developed a model of care “I-TREC” entirely calibrated for implementation within the current health system across all facility types (Primary Health Centre, Community Health Centre, and District Hospital) in a block in Shaheed Bhagat Singh (SBS) Nagar district of Punjab, India. We undertook an academic-community partnership to incorporate the combination of a CDSS with task-shifting into the GoI CPHC-NCD system, a platform that assists healthcare providers to record patient information for routine NCD care. Academic partners developed clinical algorithms, a revised clinic workflow, and provider training modules with iterative collaboration and consultation with government and technology partners to incorporate CDSS within the existing system. Discussion The CDSS-enabled GoI CPHC-NCD system provides evidence-based recommendations for hypertension and diabetes; threshold-based prompts to assure referral mechanism across health facilities; integrated patient database, and care coordination through workflow management and dashboard alerts. To enable efficient implementation, modifications were made in the patient workflow and the fulcrum of the use of technology shifted from physician to nurse. Conclusion Designed to be applicable nationwide, the I-TREC model of care is being piloted in a block in the state of Punjab, India. Learnings from I-TREC will provide a roadmap to other public health experts to integrate and adapt their interventions at the national level. Trial registration CTRI/2020/01/022723.

Community detection is becoming a highly demanded topic in social networking-based applications. It involves finding the maximum intraconnected and minimum inter-connected sub-graphs in given social networks. Many approaches have been developed for community’s detection and less of them have focused on the dynamical aspect of the social network. The decision of the community has to consider the pattern of changes in the social network and to be smooth enough. This is to enable smooth operation for other community detection dependent application. Unlike dynamical community detection Algorithms, this article presents a non-dominated aware searching Algorithm designated as non-dominated sorting based community detection with dynamical awareness (NDS-CD-DA). The Algorithm uses a non-dominated sorting genetic algorithm NSGA-II with two objectives: modularity and normalized mutual information (NMI). Experimental results on synthetic networks and real-world social network datasets have been compared with classical genetic with a single objective and has been shown to provide superiority in terms of the domination as well as the convergence. NDS-CD-DA has accomplished a domination percentage of 100% over dynamic evolutionary community searching DECS for almost all iterations.

IntroductionHeart failure (HF) is a major contributor to cardiovascular morbidity and mortality in people with diabetes. In this study, we estimated trends in the incidence of HF inpatient admissions and emergency department (ED) visits by diabetes status.Research design and methodsPopulation-based age-standardized HF rates in adults with and without diabetes were estimated from the 2006–2017 National Inpatient Sample, Nationwide ED Sample and year-matched National Health Interview Survey, and stratified by age and sex. Trends were assessed using Joinpoint.ResultsHF inpatient admissions did not change in adults with diabetes between 2006 and 2013 (from 53.9 to 50.4 per 1000 persons; annual percent change (APC): −0.3 (95% CI −2.5 to 1.9) but increased from 50.4 to 62.3 between 2013 and 2017 (APC: 4.8 (95% CI 0.3 to 9.6)). In adults without diabetes, inpatient admissions initially declined (from 14.8 in 2006 to 12.9 in 2014; APC −2.3 (95% CI −3.2 to –1.2)) and then plateaued. Patterns were similar in men and women, but relative increases were greatest in young adults with diabetes. HF-related ED visits increased overall, in men and women, and in all age groups, but increases were greater in adults with (vs without) diabetes.ConclusionsCauses of increased HF rates in hospital settings are unknown, and more detailed data are needed to investigate the aetiology and determine prevention strategies, particularly among adults with diabetes and especially young adults with diabetes.

Integrating cardiovascular disease (CVD) prevention in routine HIV care remains a challenge. This study aimed to identify factors associated with adherence to guideline-recommended CVD preventive practices among HIV clinicians. Clinicians from eight HIV clinics in Atlanta were invited to complete an online survey. The survey was informed by the Consolidated Framework for Implementation Research and assessed the following: clinician CVD risk screening and advice frequency (never to always), individual characteristics (clinician beliefs, self-efficacy, and motivation), inner setting factors (clinic culture, learning climate, leadership engagement, and resources available), and outer setting factors (peer pressure and patient needs). Bivariate correlations examined associations between these factors and guideline adherence. Thirty-eight clinicians completed the survey (82% women, mean age 42 years, 50% infectious disease physicians). For risk screening, clinicians always check patient blood pressure (median score 7.0/7), while they usually ask about smoking or check their blood glucose (median score 6.0/7). For advice provision, clinicians usually recommend quitting smoking, controlling cholesterol or controlling blood pressure (median score 6.0/7), while they often recommend controlling blood glucose, losing weight, or improving diet/physical activity (median score 5.5/7). Clinician beliefs, motivation and self-efficacy were positively correlated with screening and advice practices (r = .55−.84), while inner setting factors negatively correlated with lifestyle-related screening and advice practices (r = −.51 to −.76). Peer pressure was positively correlated with screening and advice practices (r = .57–.89). Clinician psychosocial characteristics and perceived peer pressure positively influence adherence to guideline-recommended CVD preventive practices. These correlates along with leadership engagement could be targeted with proven implementation strategies.

Supplemental Digital Content is available in the text., Background: An epidemic of chronic kidney disease is occurring in rural communities in low-income and middle-income countries that do not share common kidney disease risk factors such as diabetes and hypertension. This chronic kidney disease of unknown etiology occurs primarily in agricultural communities in Central America and South Asia. Consequently, environmental risk factors including heat stress, heavy metals exposure, and low altitude have been hypothesized as risk factors. We conducted an environmental epidemiological analysis investigating these exposures in India which reports the disease. Methods: We used a random sample population in rural and urban sites in Northern and Southern India in 2010, 2011, and 2014 (n = 11,119). We investigated associations of the heat index, altitude, and vicinity to cropland with estimated glomerular filtration rate (eGFR) using satellite-derived data assigned to residential coordinates. We modeled these exposures with eGFR using logistic regression to estimate the risk of low eGFR, and linear mixed models (LMMs) to analyze site-specific eGFR-environment associations. Results: Being over 55 years of age, male, and living in proximity to cropland was associated with increased risk of low eGFR [odds ratio (OR) (95% confidence interval (CI) = 2.24 (1.43, 3.56), 2.32 (1.39, 3.88), and 1.47 (1.16, 2.36)], respectively. In LMMs, vicinity to cropland was associated with low eGFR [−0.80 (−0.44, −0.14)]. No associations were observed with temperature or altitude. Conclusions: Older age, being male, and living in proximity to cropland were negatively associated with eGFR. These analyses are important in identifying subcommunities at higher risk and can help direct future environmental investigations.

Antibody secreting cells (ASC) are the effectors of protective humoral immunity and the only cell type that produces antibodies or immunoglobulins in mammals. In addition to their formidable capacity to secrete massive quantities of proteins, ASC are terminally-differentiated and have unique features to become long-lived plasma cells (LLPC). Upon antigen encounter, B cells are activated through a complex multistep process to undergo fundamental morphological, subcellular, and molecular transformation to become an efficient protein factory with life-long potential. The ASC survival potential is determined by factors at the time of induction, capacity to migration from induction to survival sites, and ability to mature in the specialized bone marrow microenvironments. In the past decade, considerable progress has been made in identifying factors regulating ASC longevity. Here, we review the intrinsic drivers, trafficking signals, and extrinsic regulators with particular focus on how they impact the survival potential to become a LLPC.

Brachial plexus block has been gained popularity after its introduction because of provision of quality anesthesia and optimal postoperative analgesia in upper arm surgeries, and introduction of ultrasound guidance in recent years further enhances the practice because of efficacy and safety of procedure. This retrospective observational study evaluated the outcome and safety of ultrasound-guided brachial plexus block (supraclavicular and interscalene approach) in a tertiary care hospital of Bangladesh over 3-years period (January 2017 to December 2019) through analyzing preoperative anesthesia evaluation form, anesthesia documents and postoperative records. 113 patients were covered during the study period, of which 59 (52.2%) were males and 54 (47.8%) were females. Mean age of the patients were 38.94 ± 20.37 years. Majority of the patients (63.7%) were in ASA grading I. Operative time for surgeries were 115.30 ± 35.19 minutes. duration of sensory and motor block were 618 ± 55 minutes and 450 ± 74 minutes respectively. And first dose of postoperative analgesic was given after 705 ± 94 minutes of surgery. Tachycardia and hypertension were observed in 4.4% patients, where failure of motor blockade and puncture of subclavian vein were recoreded 1.8% and 0.9% respectively. Current study found that with ultrasound guidance in skilled hands, brachial plexus blockade through combination of supraclavicular and interscalene approaches can provide quality anesthesia and analgesia with minimal complications.

OBJECTIVE To examine changes in and the relationships between diabetes management and rural and urban residence. RESEARCH DESIGN AND METHODS Using National Health and Nutrition Examination Survey (1999–2018) data from 6,372 adults aged ≥18 years with self-reported diagnosed diabetes, we examined poor ABCS: A1C >9% (>75 mmol/mol), Blood pressure (BP) ≥140/90 mmHg, Cholesterol (non-HDL) ≥160 mg/dL (≥4.1 mmol/L), and current Smoking. We compared odds of urban versus rural residents (census tract population size ≥2,500 considered urban, otherwise rural) having poor ABCS across time (1999–2006, 2007–2012, and 2013–2018), overall and by sociodemographic and clinical characteristics. RESULTS During 1999–2018, the proportion of U.S. adults with diabetes residing in rural areas ranged between 15% and 19.5%. In 1999–2006, there were no statistically significant rural-urban differences in poor ABCS. However, from 1999–2006 to 2013–2018, there were greater improvements for urban adults with diabetes than for rural for BP ≥140/90 mmHg (relative odds ratio [OR] 0.8, 95% CI 0.6–0.9) and non-HDL ≥160 mg/dL (≥4.1 mmol/L) (relative OR 0.45, 0.4–0.5). These differences remained statistically significant after adjustment for race/ethnicity, education, poverty levels, and clinical characteristics. Yet, over the 1999–2018 time period, minority race/ethnicity, lower education attainment, poverty, and lack of health insurance coverage were factors associated with poorer A, B, C, or S in urban adults compared with their rural counterparts. CONCLUSIONS Over two decades, rural U.S. adults with diabetes have had less improvement in BP and cholesterol control. In addition, rural-urban differences exist across sociodemographic groups, suggesting that efforts to narrow this divide may need to address both socioeconomic and clinical aspects of care.

There are scarce data on trends in potentially preventable emergency department (ED) use among adults with diabetes. Using data from the National Emergency Department Database and American Community Survey, we estimated percent change in rates of ED visits for diabetes-related Ambulatory Care Sensitive Conditions (ACSCs) (short-term complications [STC], long-term complications [LTC], uncontrolled diabetes, and lower extremity ulcer and inflammation [LEUI]) per 100,00 persons over 2008-2014 by age, sex, rural/urban status, region, and insurance. We identified visits using the presence of relevant ICD-9 codes for primary diagnoses. Overall rates of ED visits increased for STC (by 60.0%), uncontrolled diabetes (27.4%), and LEUI (35.5%) (Table 1). These increases were observed across all age groups with greatest increases in those 45-64 years, but were not substantially different by gender, rural/urban, region, or insurance type. Overall rates of ED visits for LTC decreased by 8.7%, with the greatest decreases among older, rural, Northeastern, and Medicare and privately-insured adults. These results imply ambulatory diabetes management prior to the Affordable Care Act successfully reduced ED use for LTC over 2008-14, but not for other outcomes, especially for middle-aged populations. Disclosure T. S. Uppal: Stock/Shareholder; Self; Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Mesoblast Ltd. G. Fernandes: Employee; Self; Merck & Co., Inc., Employee; Spouse/Partner; Janssen Research & Development, LLC, Stock/Shareholder; Self; Merck & Co., Inc., Stock/Shareholder; Spouse/Partner; Janssen Research & Development, LLC. J. Haw: None. M. K. Shah: None. S. Turbow: Research Support; Self; Merck & Co., Inc. P. K. Chehal: None. S. Rajpathak: Employee; Self; Merck Sharp & Dohme Corp. K. Narayan: None. M. K. Ali: Advisory Panel; Self; Bayer Inc., Other Relationship; Self; Merck & Co., Inc.

Background and aims Neutrophil elastase and myeloperoxidase enzymes protect us from infection by killing pathogens. However, exaggerated activities of these enzymes can induce tissue damage, inflammation and oxidative stress. The present study was aimed to explore the expressions of neutrophil elastase and myeloperoxidase mRNA in the peripheral blood leukocytes (PBL) in patients with newly diagnosed type 2 diabetes mellitus. Methods In this cross-sectional study, 104 participants including 65 normoglycemic control subjects and 39 newly diagnosed type 2 diabetes patients were recruited. Glycemic and metabolic markers were evaluated from fasting blood samples. The mRNA levels of neutrophil elastase and myeloperoxidase genes in the PBL were quantified by real-time quantitative PCR. Results Compared to control subjects, diabetes patients showed a significant down regulation of both neutrophil elastase (p = 0.039) and myeloperoxidase (p = 0.023) mRNA expressions in the PBL. The neutrophil elastase and myeloperoxidase mRNA levels showed a negative trend with fasting glucose levels but did not show any significant correlations with HbA1c, insulin level, insulin resistance or sensitivity status. Conclusions It was concluded that type 2 diabetes mellitus is associated with a decrease in neutrophil elastase and myeloperoxidase gene expression in the PBL.

We tested the hypothesis that 17α-hydroxyprogesterone caproate (17α-OHP-C) may decrease preterm delivery (PTD) in women with placenta praevia. This was a randomised controlled trial included 114 women with placenta praevia (between 24 and 28 weeks). They were randomly assigned to group I (17α-OHP-C) who received weekly injection of 17α-OHP-C (250 mg/IM) till completing 37 weeks' gestation or group II (Non 17α-OHP-C). The percentage of placenta praevia patients went into PTD in the 17α-OHP-C group was significantly less in comparison to the PTD in the Non 17α-OHP-C group (∼37%

OBJECTIVES: To estimate the pooled relative risk of incident acute myocardial infraction (AMI) among HIV-infected adults compared to HIV-uninfected controls and explore the contribution of traditional and HIV-related risk factors. BACKGROUND: Understanding AMI risk and associated risk factors in HIV-infected populations has the potential to inform clinical management and prevention strategies. METHODS: We systematically identified cohort studies of HIV-infected or HIV-infected and matched uninfected adults reporting AMI incidence rates published up to January 1, 2017. Random-effects meta-analysis models were used to estimate the aggregate relative risk of AMI by HIV status. Subgroup analysis and meta-regression were used to explore factors affecting risk. RESULTS: 16 studies (N=1,619,690, median age 38.5 years, 78.9% male, mean follow-up of 6.5 years) were included. In pooled analyses of HIV-infected and matched uninfected cohorts (n=5), HIV-infected individuals had higher AMI incidence rates (absolute risk difference=2.2 cases per 1000 persons per year) and twice the risk of AMI (RR=1.96 [1.5, 2.6]) compared with matched HIV-uninfected controls. In a multivariate meta-regression, each additional percentage point in the proportion of male participants (OR=1.20 [1.14, 1.27]) and each additional percentage point in the prevalence of hypertension (OR=1.19 [1.12, 1.27]), dyslipidemia (OR=1.09 [1.07, 1.11]), and smoking (OR=1.09 [1.05, 1.13]) were independently associated with increased AMI risk in HIV-infected adults. CONCLUSIONS AND RELEVANCE: Chronic HIV infection is associated with a two-fold higher AMI risk. Traditional risk factors such as hypertension, dyslipidemia, and smoking are significant contributors to AMI risk among HIV-infected adults and should be aggressively targeted in routine HIV care.

Background: Postpartum hemorrhage (PPH) is a direct cause of maternal death all over the world. A Bakri balloon is recommended by American College of Obstetricians and Gynecologists (ACOG) and Worl...

Tendon injury is one of the most common causes of wastage in equine. The superficial digital flexor tendon (SDFT) gets affected the most, especially in the mid-metacarpal region. Several studies have focused on the grafting of severed SDFT, but no ideal grafting material has been approved for clinical application. The present study aimed to evaluate the grafting of the mid-metacarpal SDFT in donkeys with a double-layered polypropylene mesh clinically, ultrasonically, macro/microscopically. Clinically healthy adult donkeys (n = 24) were divided randomly and equally into two groups: control (C) and study (S) groups. Tenotomy was performed on all animals by excising a full-thickness segment from the mid-metacarpal SDFT. In the C group, a suture tenorrhaphy was performed. While in the S group, SDFT was grafted with the double-layered polypropylene mesh. The S group showed faster clinical improvements, and earlier appearance of normal newly formed tendinous tissue ultrasonically compared with the C group. Macroscopically, the grafted tendons showed a rapid restoration of normal color and consistency. Moreover, they had minimal peri-tendinous adhesions compared with the non-grafted tendons. Microscopically, the grafted tendons showed earlier vascularization and more mature collagen fibers compared with the non-grafted tendons. In the present study, we have succeeded to graft the gap of the mid-metacarpal SDFT of a donkey using the double-layered polypropylene mesh. This method is an economical way to accelerate the healing process of the SDFT and enhance the clinical recovery in donkeys.

ObjectivesTo determine the prevalence of cardiovascular disease (CVD) risk factors and explore associations with high-sensitivity cardiac troponin I (hscTnI) and high-sensitivity C-reactive protein (hsCRP) in people living with HIV (PLHIV) in Kenya.DesignPilot cross-sectional study.SettingData were collected from community HIV clinics across two sites in Nairobi, Kenya, from July 2019 to May 2020.ParticipantsConvenience sample of 200 PLHIV (≥30 years with no prior history of CVD).Outcome measuresPrevalence of cardiovascular risk factors and its association with hsTnI and hsCRP levels.ResultsAcross 200 PLHIV (median age 46 years, IQR 38–53; 61% women), the prevalence of hypercholesterolaemia (total cholesterol >6.1 mmol/L) and hypertension were 19% (n=30/199) and 30% (n=60/200), respectively. Smoking and diabetes prevalence was 3% (n=5/200) and 4% (n=7/200). HscTnI was below the limit of quantification (3 mg/L), intermediate (1–3 mg/L) and low (160 mm Hg (aOR 4.68, 95% CI 1.55 to 14) compared with ConclusionThe majority of PLHIV—using traditional risk estimation systems—have a low estimated CVD risk likely reflecting a younger aged population predominantly consisting of women. Hypertension and hypercholesterolaemia were common while smoking and diabetes rates remained low. While hscTnI values were associated with increasing age and raised blood pressure, no associations between hsCRP levels and traditional cardiovascular risk factors were observed.

ObjectiveDescribe trends in opioid plus high-risk medication coprescribing in the USA.DesignAnalyses of serial, cross-sectional, nationally representative data of the National Ambulatory Medical Care Survey (NAMCS) over 2007–2016 and the National Hospital Ambulatory Medical Care Survey (NHAMCS) over 2007–2018.SettingUS ambulatory (NAMCS) and emergency department (ED, NHAMCS) settings.ParticipantsPatient visits in which the patient was 18 years and older with an opioid prescription in the NAMCS or NHAMCS databases.Primary and secondary outcome measuresFrequency of opioid plus high-risk medication coprescribing.ResultsFrom a combined sample of 700 499 visits over 2007–2018, there were 105 720 visits (15.1%) where opioids were prescribed. n=31 825 were from NAMCS and n=73 895 were from NHAMCS. The mean prevalence of coprescription of opioids and high-risk medications for the combined NAMCS and NHAMCS sample was 18.4% in 2007, peaked at 33.2% in 2014 and declined to 23.8% in 2016. Compared with adults receiving opioid prescriptions alone, those coprescribed opioids and high-risk medications were older, more likely female, white and using private or Medicare insurance (pConclusionsCoprescribing is more common in ambulatory than ED settings and has been declining, yet one in four patient visits where opioids were prescribed resulted in coprescribed, high-risk medications in 2016. Efforts and research to help lower the rates of high-risk prescribing are needed.

Background The prevalence of moderate or complex (moderate-complex) congenital heart defects (CHDs) among adults is increasing due to improved survival, but many patients experience lapses in specialty care or their CHDs are undocumented in the medical system. There is, to date, no efficient approach to identify this population. Objective To develop and assess the performance of a risk score to identify adults aged 20-60 years with undocumented specific moderate-complex CHDs from electronic health records (EHR). Methods We used a case-control study (596 adults with specific moderate-complex CHDs and 2384 controls). We extracted age, race/ethnicity, electrocardiogram (EKG), and blood tests from routine outpatient visits (1/2009 through 12/2012). We used multivariable logistic regression models and a split-sample (4: 1 ratio) approach to develop and internally validate the risk score, respectively. We generated receiver operating characteristic (ROC) c-statistics and Brier scores to assess the ability of models to predict the presence of specific moderate-complex CHDs. Results Out of six models, the non-blood biomarker model that included age, sex, and EKG parameters offered a high ROC c-statistic of 0.96 [95% confidence interval: 0.95, 0.97] and low Brier score (0.05) relative to the other models. The adult moderate-complex congenital heart defect risk score demonstrated good accuracy with 96.4% sensitivity and 80.0% specificity at a threshold score of 10. Conclusions A simple risk score based on age, sex, and EKG parameters offers early proof of concept and may help accurately identify adults with specific moderate-complex CHDs from routine EHR systems who may benefit from specialty care.

Aims We assessed costs and cost-effectiveness of implementing Fit Body and Soul (FBAS), a church-based 18-session lifestyle education intervention for African Americans. Methods We calculated incremental cost-effectiveness ratios (ICER) using data from a cluster randomized controlled trial comparing FBAS with health education (HE) among 604 overweight participants in 20 churches. The ICER was the adjusted difference in costs to deliver FBAS versus HE over the difference in weight change (kilograms [kg]) at one-year follow-up. Costs included those incurred for participant identification and program implementation. We fitted linear mixed-effects regression models, accounting for clustering of participants within churches and for age, sex, and educational attainment. We repeated these analyses for secondary outcomes (waist circumference [cm], physical activity [MET], glucose, blood pressure, and quality of life). Results Per-person intervention cost of FBAS was $50.39 more than HE ($442.22 vs. $391.83 per-person), and adjusted differences in weight change (1.9 kg [95% CI: 1.0 to 2.8]) and waist circumference (2.4 cm [95% CI: 1.3 to 3.4]) were both significant. FBAS did not result in statistically significant differences in physical activity, glucose, blood pressures, or quality of life. We estimated that compared to HE, FBAS costs an additional $26.52 per kg weight lost and $21.00 per cm reduction in waist circumference. Conclusions For a modest increase in cost, FBAS led to greater weight and waist reductions among African Americans in a church setting. ClinicalTrials.gov Identifier NCT01730196 .

Antibody secreting cells (ASC) circulate after vaccination and migrate to the bone marrow (BM) where a subset known as long-lived plasma cells (LLPC) persist and secrete antibodies for a lifetime. The mechanisms of how circulating ASC become LLPC are not well elucidated. Here, we show that human blood ASCs have distinct morphology, transcriptomes, and epigenetics compared to BM LLPC. LLPC acquire transcriptional and epigenetic changes in the apoptosis pathway to support their survival. Upregulation of pro-survival gene expression accompanies downregulation of pro-apoptotic gene expression in LLPC. While pro-apoptotic gene loci are less accessible, pro-survival gene loci are not always accompanied by accessibility changes. Importantly, we show similar LLPC morphological and transcriptional maturation of blood ASC in response to the novel in vitro BM mimetic. In all, our study demonstrates that blood ASC in the BM microniche must undergo morphological and molecular changes to mature into apoptotic-resistant LLPC.

BackgroundPostoperative pain remains a challenging problem, which requires a dynamic approach using a variety of treatment modalities to obtain an optimal outcome with respect to enhancing patient comfort and facilitating the recovery process. Multimodal analgesia signifies an increasingly popular approach to prevent postoperative pain. The approach includes administering a combination of opioid and nonopioid analgesics that act at different sites within the central and peripheral nervous systems in an effort to improve pain control while eliminating opioid-related adverse effects.Materials and MethodsTo understand the perception and attitude of 4th year medical students, a structured questionnaire survey was done among six different medical colleges including government (Armed Forces Medical College, Cumilla Medical College and Colonel Malek Medical College, Manikganj) and non-government medical colleges (Army Medical College Bogura, Brahmanbaria Medical College and Chattogram International Medical College) of Bangladesh in October 2019. Total 340 students participated in the study.ResultAmong the 340 students, almost 336 (98.2%) students were agreed that postoperative pain management is an essential element of patient care. Only 4 (1.18%) respondents disagreed. On the other hand, regarding its influence on early recovery and reduction of hospital staying, 311 (91.47%) respondents agreed and 29 (8.53%) respondents were found as disagreed. Regarding the issue of opioid commonly induced respiratory depression, 257 (75.59%) respondents thought it is a common adverse event and 81 (23.82%) respondents disagreed. 206 (60.59%) respondents didn’t agree that opioid always produce addiction or tolerance and 134 (39.71%) respondents disagreed with the same issue. 294 (86) respondents agreed that multimodal analgesia increases patient’s cost and 46 (14%) disagreed. 249 (74%) students agreed that regional techniques are useful for postoperative pain management and 89 (26%) respondents disagreed.ConclusionAdequate post-operative pain management knowledge is necessary to reduce post-operative complications.

Cell proliferation and survival require continuous ribosome biogenesis and protein synthesis. Genes encoding ribosomal RNA are physically located in a specialized substructure within the nucleus known as the nucleolus, which has a central role in the biogenesis of ribosomes. Matrix metalloproteinase-2 was previously detected in the nucleus, however, its role there is elusive. Herein we report that matrix metalloproteinase-2 resides within the nucleolus to regulate ribosomal RNA transcription. Matrix metalloproteinase-2 is enriched at the promoter region of ribosomal RNA gene repeats, and its inhibition downregulates preribosomal RNA transcription. The N-terminal tail of histone H3 is clipped by matrix metalloproteinase-2 in the nucleolus, which is associated with increased ribosomal RNA transcription. Knocking down/out matrix metalloproteinase-2, or inhibiting its activity, prevents histone H3 cleavage and reduces both ribosomal RNA transcription and cell proliferation. In addition to the known extracellular roles of matrix metalloproteinase-2 in tumor growth, our data reveal an epigenetic mechanism whereby intranucleolar matrix metalloproteinase-2 regulates cell proliferation through histone clipping and facilitation of ribosomal RNA transcription.

BackgroundControlling and managing hypertension is a highly dynamic process yet, to our knowledge, existing evidence on hypertension control gaps in middle-income countries (MICs) is largely based on cross-sectional data. We provide the first longitudinal investigation of how individuals with hypertension move through the care continuum over time across multiple MICs.MethodsWe used multiple waves of population-based longitudinal cohort data from China, Indonesia, Mexico and South Africa. Based on measured blood pressure and information on hypertension diagnosis and treatment status, we classified adults aged 40 + into four care stages at both the baseline and follow-up waves: undiagnosed; diagnosed and untreated; diagnosed, treated, but uncontrolled (systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg); diagnosed, treated, and controlled (SBP < 140 mmHg and DBP < 90 mmHg). We estimated the probability of individuals progressing forward or regressing backwards through the continuum over a five-to nine-year between-wave period and investigated how these probabilities varied by age, sex, household location and educational attainment using Poisson regression models. We also estimated the probabilities of important clinical transitions (e.g. becoming diagnosed or treated; achieving blood pressure control; discontinuing treatment and losing blood pressure control).FindingsOur data included 8359 individuals with hypertension (China: N=1371, Indonesia: N= 3438, Mexico: N=1946, South Africa: N=1604). Across all countries, there was a less than 50% probability of forward progression through the care continuum over time. Just over one in four undiagnosed individuals became diagnosed (China 30% [95% CI 26-33%], Indonesia 30% [95% CI 28-32%], Mexico 27% [95% CI 25-29%], South Africa 37% [95% CI 34-39%]) and one in three diagnosed, untreated individuals became treated (Indonesia 17% [95% CI 14-21%], Mexico 30% [95% CI 28-32%], China 48% [95% CI 39-56%], South Africa 42% [95% CI 40-44%]). Importantly, there were very high probabilities of regressing to less advanced continuum stages: up to nine in ten treated and controlled individuals lost blood pressure control (Indonesia 92% [95% CI 88-95%], Mexico 77% [95% CI 72-81%], China 76% [95% CI 68-83%], South Africa 48% [95% CI 42-54%]) and up to three in four individuals discontinued treatment over the follow-up period (China 36% [95% CI 32-41%], Indonesia 70% [95% CI 67-73%], Mexico 34% [5% CI 32-36%], South Africa 25% [23-27%]). Individuals from rural households were disadvantaged in all countries but China, while females were more likely to progress through the continuum in Indonesia and Mexico.InterpretationOur results uncover critical gaps in hypertension care in MICs in both early and late stages of the continuum. Adopting a longitudinal perspective reveals that policies solely aimed at improving diagnosis or initiating treatment may not lead to large improvements in control, as treatment initiation rates are low and achievement of blood pressure control and adherence to therapy are rarely sustained over time.RESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for articles published from database inception until January 1st, 2021 using variations of the search terms “blood pressure”, “hypertension”, “continuum”, “cascade”, “treatment”, “diagnosis”, “control”, “treated”, “diagnosed”, “controlled” to screen titles and abstracts. The currently largest studies estimating nationally representative levels of hypertension diagnosis, treatment and control across multiple low- and middle-income countries (LMICs) are the Prospective Urban Rural Epidemiology (PURE) study from 2013, which included 140 000 individuals across 14 LMICs and a more recent study based on 1·1 million adults in 44 LMICs from 2019. Both studies highlight important gaps in awareness, diagnosis, treatment and control of hypertension across populations in LMICs. However, these and smaller non-nationally representative or single country studies are all based on cross-sectional data and none capture the dynamic nature of chronic disease care and how individuals move through the hypertension care continuum over time.Added value of this studyTo our knowledge, we provide the first longitudinal evidence on how individuals with hypertension in middle-income countries (MICs) move through the hypertension care continuum over time using country-wide, longitudinal cohort data from four MICs, which span three different continents and account for close to one-fourth of the world population. The longitudinal perspective provides new insights over existing cross-sectional cascades by capturing critical dynamic elements of chronic disease management, such as how individuals arrived at a specific continuum stage or whether they move forward or backward through continuum stages over time.Implications of all available evidenceOur results reveal that individuals rarely sustain blood pressure control and that they tend to discontinue treatment over time. These results can inform efforts to improve hypertension control by revealing the need to move beyond policies aimed solely at screening and diagnosis to those that also aim to help individuals sustain blood pressure control over time.

Cardiovascular disease (CVD) is the leading cause of mortality in South Asia, with rapidly increasing prevalence of hypertension, type 2 diabetes (T2DM) and hyperlipidemia over the last two decades. Atherosclerotic CVD (ASCVD) affects South Asians earlier in life and at lower body weights, which is not fully explained by differential burden of conventional risk factors. Heart failure (HF) is a complex clinical syndrome of heterogeneous structural phenotypes including two major clinical subtypes, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). The prevalence of HF in South Asians is also rising with other metabolic diseases, and HFpEF develops at younger age and leaner body mass index in South Asians than in Whites. Recent genome-wide association studies, epigenome-wide association studies and metabolomic studies of ASCVD and HF have identified genes, metabolites and pathways associated with CVD traits. However, these findings were mostly driven by samples of European ancestry, which may not accurately represent the CVD risk at the molecular level, and the unique risk profile of CVD in South Asians. Such bias, while formulating hypothesis-driven research studies, risks missing important causal or predictive factors unique to South Asians. Importantly, a longitudinal design of multi-omic markers can capture the life-course risk and natural history related to CVD, and partially disentangle putative causal relationship between risk factors, multi-omic markers and subclinical and clinical ASCVD and HF. In conclusion, combining high-resolution untargeted metabolomics with epigenomics of rigorous, longitudinal design will provide comprehensive unbiased molecular characterization of subclinical and clinical CVD among South Asians. A thorough understanding of CVD-associated metabolomic profiles, together with advances in epigenomics and genomics, will lead to more accurate estimates of CVD progression and stimulate new strategies for improving cardiovascular health.

Several interventions have been found to be effective for reversing prediabetes in adults. This systematic review and meta-analysis aims to compare the effectiveness of such interventions.MEDLINE, Embase, and Cochrane Library databases were searched for articles published between January 1, 2000 and June 27, 2018. RCTs in adults with prediabetes, testing nonsurgical interventions lasting for ≥3 months, and reporting the number of participants achieving normal glucose levels at intervention end were eligible. The pooled risk difference and number needed to treat for achieving normoglycemia were estimated using a random-effects, arm-based network meta-analysis. The strength of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Data were obtained in 2018 and analyzed in 2019 and 2021.Of 54 studies included in the systematic review, 47 were meta-analyzed (n=26,460, mean age=53 years, 46% male, 31% White). Studies included 27 arms testing lifestyle modification interventions, 25 testing medications, 5 testing dietary supplements, and 10 testing Chinese medicine. There were 35 control/placebo arms. At a median follow-up of 1.6 years, more participants in the lifestyle modification groups achieved normoglycemia than those in the control (risk difference=0.18, number needed to treat=6). The strength of the evidence was strong for lifestyle modification. Over a median follow-up of 2.7 years, more participants receiving glucagon-like peptide-1 receptor agonists (risk difference=0.47, number needed to treat=2), α-glucosidase inhibitors (risk difference=0.29, number needed to treat=4), and insulin sensitizers (risk difference=0.23, number needed to treat=4) achieved normoglycemia than control. The strength of evidence was moderate for these medications.Although several pharmacological approaches can reverse prediabetes, lifestyle modification provides the strongest evidence of effectiveness and should remain the recommended approach to address this condition.

This study investigated whether the predictive ability of the Finnish Diabetes Risk Score (FINDRISC) can be improved among people with HIV by adding a marker of insulin resistance. In this longitudinal analysis of the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study, HIV-positive and HIV-negative participants without prevalent diabetes were included. FINDRISC score and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were calculated at baseline. Cox proportional hazards models were used to examine associations between baseline risk scores and time to incident diabetes (first self-report of diabetes medication use). Model discrimination (Uno's c-statistic) and calibration (observed vs. cumulative probability of diabetes) were assessed for FINDRISC, HOMA-IR, and combined FINDRISC and HOMA-IR. Overall, 2,527 men (1,299 HIV-positive and 1,228 HIV-negative, median age = 44) and 2,446 women (1,841 HIV-positive and 605 HIV-negative, median age = 41) were included. Over 47,040 person-years of follow-up, diabetes incidence rates per 1,000 person-years were 9.5 in HIV-positive men, 7.1 in HIV-negative men, 14.5 in HIV-positive women, and 15.1 in HIV-negative women. FINDRISC discrimination (HIV-positive men c = 0.64 [0.55, 0.74], HIV-negative men c = 0.74 [0.68, 0.79], HIV-positive women c = 0.68 [0.64, 0.71], and HIV-negative women c = 0.73 [0.66, 0.79]) was significantly better than that of HOMA-IR. FINDRISC was better calibrated than HOMA-IR in each of the four groups. Adding HOMA-IR did not improve FINDRISC discrimination/calibration. Diabetes risk prediction with FINDRISC was suboptimal in men and women with HIV, and its performance was not improved with addition of HOMA-IR. The optimal method for identifying people living with HIV at-risk for diabetes is yet to be identified.

BACKGROUND The COVID-19 pandemic has required clinicians to pivot to offering services via telehealth; however, it is unclear which patients (users of care) are equipped to use digital health. This is especially pertinent for adults managing chronic diseases, such as obesity, hypertension, and diabetes, which require regular follow-up, medication management, and self-monitoring. OBJECTIVE The aim of this study is to measure the trends and assess factors affecting health information technology (HIT) use among members of the US population with and without cardiovascular risk factors. METHODS We used serial cross-sectional data from the National Health Interview Survey for the years 2012-2018 to assess trends in HIT use among adults, stratified by age and cardiovascular risk factor status. We developed multivariate logistic regression models adjusted for age, sex, race, insurance status, marital status, geographic region, and perceived health status to assess the likelihood of HIT use among patients with and without cardiovascular disease risk factors. RESULTS A total of 14,304 (44.6%) and 14,644 (58.7%) participants reported using HIT in 2012 and 2018, respectively. When comparing the rates of HIT use for the years 2012 and 2018, among participants without cardiovascular risk factors, the HIT use proportion increased from 51.1% to 65.8%; among those with one risk factor, it increased from 43.9% to 59%; and among those with more than one risk factor, it increased from 41.3% to 54.7%. Increasing trends in HIT use were highest among adults aged >65 years (annual percentage change [APC] 8.3%), who had more than one cardiovascular risk factor (APC 5%) and among those who did not graduate from high school (APC 8.8%). Likelihood of HIT use was significantly higher in individuals who were younger, female, and non-Hispanic White; had higher education and income; were married; and reported very good or excellent health status. In 2018, college graduates were 7.18 (95% CI 5.86-8.79), 6.25 (95% CI 5.02-7.78), or 7.80 (95% CI 5.87-10.36) times more likely to use HIT compared to adults without high school education among people with multiple cardiovascular risk factors, one cardiovascular risk factor, or no cardiovascular risk factors, respectively. CONCLUSIONS Over 2012-2018, HIT use increased nationally, with greater use noted among younger and higher educated US adults. Targeted strategies are needed to engage wider age, racial, education, and socioeconomic groups by lowering barriers to HIT access and use.

The pattern of dyslipidaemia in South Asia is believed to be different from that in other parts of the world. Nonetheless, limited population-based data are available from the region. We assessed the prevalence, types of, and factors associated with dyslipidaemia among South Asians.. We used baseline data (2010-11) of the Center for Cardiometabolic Risk Reduction in South Asia (CARRS) cohort of 16 287 representative urban adults aged ≥20 years from Chennai and Delhi in India and Karachi in Pakistan. Total cholesterol (TC) was measured by the enzymatic-cholesterol oxidase peroxidase method, high-density lipoprotein-cholesterol (HDL-C) by the direct homogeneous method and triglycerides (TG) by enzymatic methods. Low-density lipoprotein-cholesterol (LDL-C) was calculated using Friedewald's formula. We defined high TC ≥200 mg/dl or on medication; hypertriglyceridaemia ≥150 mg/dl, high LDL-C ≥130 mg/dl or on medication and low HDL-C40 mg/dl for males,50 mg/dl for females. Multivariate logistic regression was carried out to assess the factors associated with dyslipidaemia.. The prevalence of any dyslipidaemia was 76.4%, 64.3% and 68.5% among males and 89.3%, 74.4% and 79.4% among females in Chennai, Delhi and Karachi, respectively. The prevalence of elevated TC was higher in Chennai compared to Delhi and Karachi (31.3%, 28.8% and 22.9%, respectively); males had a significantly greater prevalence of high TG, whereas females had a greater prevalence of low HDL-C in all the three cities. The most common lipid abnormality in all three cities was low HDL-C, which was seen in 67.1%, 49.7% and 61.3% in Chennai, Delhi and Karachi, respectively. Only 2% of the participants were on lipid-lowering drugs. Adjusted for other factors, dyslipidaemia was positively associated with age, female sex, obesity, hypertension, diabetes and tobacco use.. Overall, almost seven in ten adults in urban South Asia have some form of dyslipidaemia, and the predominant subtypes were low HDL-C and high TG.

OBJECTIVE We investigated the risk of depression and anxiety in people whose spouse did or did not have diabetes. We also examined associations between depression and anxiety and severity of spouse’s diabetes. RESEARCH DESIGN AND METHODS We analyzed prospective self-reported data about diagnosed depression/anxiety and diabetes in cohabiting couples in the national Panel Study of Income Dynamics (PSID) during 1999–2017 (n = 13,500, 128,833 person-years of follow-up, median follow-up 8.1 years). We used Poisson models to estimate incidence and incidence rate ratios (IRRs) of depression/anxiety, according to spouse’s diabetes status overall and by severity of diabetes. RESULTS Age-, sex-, and race-adjusted incidence of depression/anxiety was 8.0/1,000 person-years (95% CI 6.5, 9.6) among those whose spouse had diabetes and 6.5/1,000 person-years (95% CI 6.0, 6.9) among those whose spouse did not have diabetes. Those whose spouse had diabetes had higher risk of depression/anxiety (IRR 1.24 [95% CI 1.01, 1.53]). Those whose spouse had diabetes-related limitations in daily activities (IRR 1.89 [95% CI 1.35, 2.67]) and diabetes combined with other chronic conditions (IRR 2.34 [95% CI 1.78, 3.09]) were more likely to develop depression/anxiety, while those whose spouse had diabetes with no limitations or additional chronic conditions had incidence of depression/anxiety similar to that of subjects whose spouses did not have diabetes. CONCLUSIONS People living with a spouse with diabetes are at higher risk of developing depression/anxiety than people whose spouse does not have diabetes; this risk is driven by the severity of the spouse’s diabetes. Strategies to address the impacts of diabetes on families need to be devised and tested.

This work proposes a dual-mode radio frequency (RF) power amplifier (PA) for the 4.8 GHz multi-standard applications using a 130 nm CMOS technology. The proposed RF power amplifier (PA) consists of two stages (driver and power). By changing the driver and the power stages bias voltages any mode of PA (class-AB∖F) can be achieved. The class-AB or linear mode power amplifier design is appropriate for IoT, LTE, 5G, and multi-standard RF transmitters. Whereas the class-F or switching mode PA is suitable for IoT-LPWAN and Bluetooth applications. The class-AB mode has a saturated output power of 23 dBm at 4.8 GHz, a power-added efficiency (PAE) of 29.5 %, an output third-order intercept point (OIP3) equals 18 dBm, and for LTE 15MHz channel bandwidth the adjacent channel power ratio (ACPR) is -36 dBc. On the other hand, the maximum PAE is 28% and the output power equals 22.3 dBm for the class-F mode. The proposed power amplifier occupies 0.88 mm2 of the chip area where the active area equals 0.53 mm2. The power dissipation is 136 mW or 26 mW in the proposed class-AB or class-F PA modes, individually.

Background People with chronic conditions are disproportionately prone to be affected by the COVID-19 pandemic but there are limited data documenting this. We aimed to assess the health, psychosocial and economic impacts of the COVID-19 pandemic on people with chronic conditions in India. Methods Between July 29, to September 12, 2020, we telephonically surveyed adults (n = 2335) with chronic conditions across four sites in India. Data on participants’ demographic, socio-economic status, comorbidities, access to health care, treatment satisfaction, self-care behaviors, employment, and income were collected using pre-tested questionnaires. We performed multivariable logistic regression analysis to examine the factors associated with difficulty in accessing medicines and worsening of diabetes or hypertension symptoms. Further, a diverse sample of 40 participants completed qualitative interviews that focused on eliciting patient’s experiences during the COVID-19 lockdowns and data analyzed using thematic analysis. Results One thousand seven hundred thirty-four individuals completed the survey (response rate = 74%). The mean (SD) age of respondents was 57.8 years (11.3) and 50% were men. During the COVID-19 lockdowns in India, 83% of participants reported difficulty in accessing healthcare, 17% faced difficulties in accessing medicines, 59% reported loss of income, 38% lost jobs, and 28% reduced fruit and vegetable consumption. In the final-adjusted regression model, rural residence (OR, 95%CI: 4.01,2.90–5.53), having diabetes (2.42, 1.81–3.25) and hypertension (1.70,1.27–2.27), and loss of income (2.30,1.62–3.26) were significantly associated with difficulty in accessing medicines. Further, difficulties in accessing medicines (3.67,2.52–5.35), and job loss (1.90,1.25–2.89) were associated with worsening of diabetes or hypertension symptoms. Qualitative data suggest most participants experienced psychosocial distress due to loss of job or income and had difficulties in accessing in-patient services. Conclusion People with chronic conditions, particularly among poor, rural, and marginalized populations, have experienced difficulties in accessing healthcare and been severely affected both socially and financially by the COVID-19 pandemic.

Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the coronavirus SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite being a respiratory illness, COVID-19 is found to increase the risk of venous and arterial thromboembolic events. Indeed, the link between COVID-19 and thrombosis is attracting attention from the broad scientific community. In this review we will analyze the current available knowledge of the association between COVID-19 and thrombosis. We will highlight mechanisms at both molecular and cellular levels that may explain this association. In addition, the article will review the antithrombotic properties of agents currently utilized or being studied in COVID-19 management. Finally, we will discuss current professional association guidance on prevention and treatment of thromboembolism associated with COVID-19.